tbuckley/cabot-search huggingface dataset:
The Crosstalk between Nephropathy and Coagulation Disorder: Pathogenesis, Treatment, and Dilemmas
Authors: Zhiwei Qiu, Xiaocong Pang, Qian Xiang, Yimin Cui
Journal: Journal of the American Society of Nephrology (2023)

The interaction between the kidney and the coagulation system greatly affects each other because of the abundant vessel distribution and blood perfusion in the kidney. Clinically, the risks of complicated thrombosis and bleeding have become important concerns in the treatment of nephropathies, especially nephrotic syndrome, CKD, ESKD, and patients with nephropathy undergoing RRTs. Adverse effects of anticoagulant or procoagulant therapies in patients with nephropathy, especially anticoagulation-related nephropathy, heparin-induced thrombocytopenia, and bleeding, seriously worsen the prognosis of patients, which have become challenges for clinicians. Over the decades, the interaction between the kidney and the coagulation system has been widely studied. However, the effects of the kidney on the coagulation system have not been systematically investigated. Although some coagulation-related proteins and signaling pathways have been shown to improve coagulation abnormalities while avoiding additional kidney damage in certain kidney diseases, their potential as anticoagulation targets in nephropathy requires further investigation. Here, we review the progression of research on the crosstalk between the coagulation system and kidney diseases and systematically analyze the significance and shortcomings of previous studies to provide new sight into future research. In addition, we highlight the status of clinical treatment for coagulation disorder and nephropathy caused by each other, indicating guidance for the formulation of therapeutic strategies or drug development.
Malaria transmission-blocking vaccines Pfs230D1-EPA and Pfs25-EPA in Alhydrogel in healthy Malian adults; a phase 1, randomised, controlled trial
Authors: Issaka Sagara, Sara A Healy, Mahamadoun H Assadou, Mamady Kone, Bruce J Swihart, Jennifer L Kwan, Jonathan Fintzi, Kourane Sissoko, Bourama Kamate, Yacouba Samake, Merepen A Guindo, M'Bouye Doucoure, Karamoko Niaré, Amagana Dolo, Balla Diarra, Kelly M Rausch, David L Narum, David S Jones, Nicholas J MacDonald, Daming Zhu, J Patrick Gorres, Alemush Imeru, Rathy Mohan, Ismaila Thera, Irfan Zaidi, Fernando Salazar-Miralles, Junhui Duan, Jillian Neal, Robert D Morrison, Olga Muratova, Daman Sylla, Elise M O'Connell, Yimin Wu, Jen C C Hume, Mamadou B Coulibaly, Charles F Anderson, Sekou F Traore, Ogobara K Doumbo, Patrick E Duffy
Journal: The Lancet Infectious Diseases (2023)
Extreme Temperature Events, Fine Particulate Matter, and Myocardial Infarction Mortality
Authors: Ruijun Xu, Suli Huang, Chunxiang Shi, Rui Wang, Tingting Liu, Yingxin Li, Yi Zheng, Ziquan Lv, Jing Wei, Hong Sun, Yuewei Liu
Journal: Circulation (2023)

Extreme temperature events (ETEs), including heat wave and cold spell, have been linked to myocardial infarction (MI) morbidity; however, their effects on MI mortality are less clear. Although ambient fine particulate matter (PM
Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes
Authors: Milton Packer, Christopher S. Wilcox, Jeffrey M. Testani
Journal: Circulation (2023)

SGLT2 (sodium-glucose cotransporter 2) inhibitors interfere with the reabsorption of glucose and sodium in the early proximal renal tubule, but the magnitude and duration of any ensuing natriuretic or diuretic effect are the result of an interplay between the degree of upregulation of SGLT2 and sodium-hydrogen exchanger 3, the extent to which downstream compensatory tubular mechanisms are activated, and (potentially) the volume set point in individual patients. A comprehensive review and synthesis of available studies reveals several renal response patterns with substantial variation across studies and clinical settings. However, the common observation is an absence of a large acute or chronic diuresis or natriuresis with these agents, either when given alone or combined with other diuretics. This limited response results from the fact that renal compensation to these drugs is rapid and nearly complete within a few days or weeks, preventing progressive volume losses. Nevertheless, the finding that fractional excretion of glucose and lithium (the latter being a marker of proximal sodium reabsorption) persists during long-term treatment with SGLT2 inhibitors indicates that pharmacological tolerance to the effects of these drugs at the level of the proximal tubule does not meaningfully occur. This persistent proximal tubular effect of SGLT2 inhibitors can be hypothesized to produce a durable improvement in the internal set point for volume homeostasis, which may become clinically important during times of fluid expansion. However, it is difficult to know whether a treatment-related change in the volume set point actually occurs or contributes to the effect of these drugs to reduce the risk of major heart failure events. SGLT2 inhibitors exert cardioprotective effects by a direct effect on cardiomyocytes that is independent of the presence of or binding to SGLT2 or the actions of these drugs on the proximal renal tubule. Nevertheless, changes in the volume set point mediated by SGLT2 inhibitors might potentially act cooperatively with the direct favorable molecular and cellular effects of these drugs on cardiomyocytes to mediate their benefits on the development and clinical course of heart failure.
Time-Dependent Prognostic Value of Serological and Measurable Residual Disease Assessments after Idecabtagene Vicleucel
Authors: Bruno Paiva, Irene Manrique, Julie Rytlewski, Timothy Campbell, Christian C. Kazanecki, Nathan Martin, Larry D. Anderson, Jesús G. Berdeja, Sagar Lonial, Noopur S. Raje, Yi Lin, Philippe Moreau, Jesús F. San-Miguel, Nikhil C. Munshi, Shari M. Kaiser
Journal: Blood Cancer Discovery (2023)

Abstract The role of measurable residual disease (MRD) in multiple myeloma patients treated with chimeric antigen receptor (CAR) T cells is uncertain. We analyzed MRD kinetics during the first year after idecabtagene vicleucel (ide-cel) infusion in 125 relapsed/refractory multiple myeloma patients enrolled in KarMMa. At month 1 after ide-cel, there were no differences in progression-free survival (PFS) between patients in less than complete response (CR) versus those in CR; only MRD status was predictive of significantly different PFS at this landmark. In patients with undetectable MRD at 3 months and beyond, PFS was longer in those achieving CR versus &amp;lt;CR. Persistent MRD in the 10−6 logarithmic range and reappearance of normal plasma cells in MRD-negative patients were associated with inferior PFS. This study unveils different prognostic implications of serological and MRD response dynamics after ide-cel and suggests the potential value of studying the reappearance of normal plasma cells as a surrogate of loss of CAR T-cell functionality. Significance: This is one of the first studies evaluating the impact of CR and MRD dynamics after CAR T therapy in relapsed/refractory multiple myeloma. These data help interpret the prognostic significance of serological and MRD responses at early and late time points after CAR T-cell infusion. See related commentary by Landgren and Kazandjian, p. 346 . This article is featured in Selected Articles from This Issue, p. 337
Research progress and application of the CRISPR/Cas9 gene-editing technology based on hepatocellular carcinoma
Authors: Shijing Yu, Ruirui Zhao, Bingchen Zhang, Chunmei Lai, Linyan Li, Jiangwen Shen, Xiarong Tan, Jingwei Shao
Journal: Asian Journal of Pharmaceutical Sciences (2023)

Hepatocellular carcinoma (HCC) is now a common cause of cancer death, with no obvious change in patient survival over the past few years. Although the traditional therapeutic modalities for HCC patients mainly involved in surgery, chemotherapy, and radiotherapy, which have achieved admirable achievements, challenges are still existed, such as drug resistance and toxicity. The emerging gene therapy of clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9-based (CRISPR/Cas9), as an alternative to traditional treatment methods, has attracted considerable attention for eradicating resistant malignant tumors and regulating multiple crucial events of target gene-editing. Recently, advances in CRISPR/Cas9-based anti-drugs are presented at the intersection of science, such as chemistry, materials science, tumor biology, and genetics. In this review, the principle as well as statues of CRISPR/Cas9 technique were introduced first to show its feasibility. Additionally, the emphasis was placed on the applications of CRISPR/Cas9 technology in therapeutic HCC. Further, a broad overview of non-viral delivery systems for the CRISPR/Cas9-based anti-drugs in HCC treatment was summarized to delineate their design, action mechanisms, and anticancer applications. Finally, the limitations and prospects of current studies were also discussed, and we hope to provide comprehensively theoretical basis for the designing of anti-drugs.
Sociodemographic and clinical characteristics associated with multiple biologic failure in psoriasis: A 2015-2022 prospective cohort analysis of the CorEvitas psoriasis registry
Authors: Joy Q. Jin, Angel Cronin, Carla Roberts-Toler, Samuel Yeroushalmi, Edward Hadeler, Riley K. Spencer, Kareem G. Elhage, George Gondo, Elizabeth B. Wallace, Soumya M. Reddy, George Han, Jessica Kaffenberger, Mitchell S. Davis, Marwa Hakimi, Jose U. Scher, April W. Armstrong, Tina Bhutani, Robert R. McLean, Wilson Liao
Journal: Journal of the American Academy of Dermatology (2023)

Psoriasis patients with poor therapeutic response to multiple biologic agents are not well-characterized.To describe the characteristics associated with development of multiple biologic failure (MBF) versus good clinical response (GR) to the first biologic.This prospective cohort analysis evaluated patients in the multicenter CorEvitas Psoriasis Registry who initiated their first biologic between 2015 and 2020 and were followed for ≥24 months. Multivariable logistic regression identified sociodemographic, clinical, and patient-reported outcomes that differed between MBF (discontinued ≥2 biologics of different classes, each used for ≥90 days, due to inadequate efficacy) and GR (continued use of first biologic for ≥2 years) patients.One thousand thirty-nine patients were analyzed (490 GR [47.2%], 65 MBF [6.3%]). Female sex, shorter psoriasis duration, earlier year of biologic initiation, prior nonbiologic systemic therapy use, history of hyperlipidemia, and Medicaid insurance were significantly associated with MBF, though the latter 2 variables exhibited wider confidence intervals, indicating a lower level of support. The first-to-second biologic sequence most observed with MBF was Tumor necrosis factor-α inhibitor to IL-17 inhibitor use.Biologic adherence between visits was not evaluated.Approximately 6% of psoriasis patients met MBF criteria. The results identify characteristics associated with MBF that may distinguish patients warranting more frequent follow-up.
Correction: ESPNIC clinical practice guidelines: intravenous maintenance fluid therapy in acute and critically ill children— a systematic review and meta-analysis
Authors: David W. Brossier, Lyvonne N. Tume, Anais R. Briant, Corinne Jotterand Chaparro, Clémence Moullet, Shancy Rooze, Sascha C. A. T. Verbruggen, Luise V. Marino, Fahad Alsohime, Sophie Beldjilali, Fabrizio Chiusolo, Leonardo Costa, Capucine Didier, Stavroula Ilia, Nyandat L. Joram, Martin C. J. Kneyber, Eva Kühlwein, Jorge Lopez, Jesus López-Herce, Huw F. Mayberry, Fortesa Mehmeti, Magdalena Mierzewska-Schmidt, Maria Miñambres Rodríguez, Claire Morice, John V. Pappachan, Florence Porcheret, Leonor Reis Boto, Luregn J. Schlapbach, Hakan Tekguc, Konstantinos Tziouvas, Jean-Jacques Parienti, Isabelle Goyer, Frederic V. Valla
Journal: Intensive Care Medicine (2023)
Atezolizumab With or Without Radiotherapy for Advanced Squamous Cell Carcinoma of the Penis (The PERICLES Study): A Phase II Trial
Authors: Hielke M. de Vries, Tynisha S. Rafael, Alberto Gil-Jimenez, Jeantine M. de Feijter, Elise Bekers, Elsbeth van der Laan, Marta Lopez-Yurda, Erik Hooijberg, Annegien Broeks, Dennis Peters, Iris M. Seignette, Floris J. Pos, Simon Horenblas, Bas W.G. van Rhijn, Ekaterina S. Jordanova, Oscar R. Brouwer, Eva Schaake, Michiel S. van der Heijden
Journal: Journal of Clinical Oncology (2023)

Patients with advanced penile squamous cell carcinoma have a poor prognosis (21% 2-year overall survival [OS] from diagnosis). We assessed the activity of atezolizumab (anti-PD-L1) in patients with advanced penile cancer, with or without radiotherapy (RT).A single-center, nonrandomized phase II study with two treatment arms was conducted in 32 patients with histologically confirmed advanced penile cancer. All patients received atezolizumab (1,200 mg) once every 3 weeks. Twenty patients, who were expected to benefit from RT for locoregional disease control, received additional irradiation. The primary end point was 1-year progression-free survival (PFS) for the complete cohort and was reached if the actual 1-year PFS was at least 35%. Secondary end points included OS, objective response rate (ORR), and tolerability. Exploratory biomarker analyses were conducted in pretreatment specimens.Median follow-up was 29.1 months (IQR, 18.1-33.5). Grade 3-4 adverse events related to atezolizumab or RT were observed in 3/32 (9.4%) and 13/20 (65%) patients, respectively. One-year PFS was 12.5% (95% CI, 5.0 to 31.3), which did not meet the study's primary end point. Median OS was 11.3 months (95% CI, 5.5 to 18.7). In the objective response-evaluable population (n = 30; 93.8%), the ORR was 16.7% (95% CI, 6 to 35), including 2 (6.7%) complete responders and 3 (10%) partial responders. Improved PFS was observed in patients with high-risk human papillomavirus (hrHPV)-positive tumors (P = .003) and those with high infiltration of intratumoral CD3+CD8+ T cells (P = .037).Although the primary end point of 1-year PFS was not met, durable antitumor activity to atezolizumab was observed in a subset of patients. Biomarkers, such as hrHPV and intratumoral CD3+CD8+ T-cell infiltration, may help to better select responders.
Pattern recognition receptor agonists in pathogen vaccines mediate antitumor T-cell cross-priming
Authors: Mark Aleynick, Judit Svensson-Arvelund, Gvantsa Pantsulaia, Kristy Kim, Samuel A Rose, Ranjan Upadhyay, Michael Yellin, Henry Marsh, Daniel Oreper, Suchit Jhunjhunwala, Christine Carine Moussion, Miriam Merad, Brian D Brown, Joshua D Brody
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Cancer immunotherapies are generally effective in patients whose tumors contain a priori primed T-cells reactive to tumor antigens (TA). One approach to prime TA-reactive T-cells is to administer immunostimulatory molecules, cells, or pathogens directly to the tumor site, that is, in situ vaccination (ISV). We recently described an ISV using Flt3L to expand and recruit dendritic cells (DC), radiotherapy to load DC with TA, and pattern recognition receptor agonists (PRRa) to activate TA-loaded DC. While ISV trials using synthetic PRRa have yielded systemic tumor regressions, the optimal method to activate DCs is unknown. Methods To discover optimal DC activators and increase access to clinical grade reagents, we assessed whether viral or bacterial components found in common pathogen vaccines are an effective source of natural PRRa ( naPRRa ). Using deep profiling (155-metric) of naPRRa immunomodulatory effects and gene editing of specific PRR, we defined specific signatures and molecular mechanisms by which naPRRa potentiate T-cell priming. Results We observed that vaccine naPRRa can be even more potent in activating Flt3L-expanded murine and human DCs than synthetic PRRa, promoting cross-priming of TA-reactive T-cells. We developed a mechanistically diverse naPRRa combination (BCG, PedvaxHIB, Rabies) and noted more potent T-cell cross-priming than with any single naPRRa. The naPRRa triplet—as part of Flt3L-primed ISV—induced greater intratumoral CD8 T-cell infiltration, T-cells reactive to a newly defined tumorous neoantigen, durable tumor regressions. Conclusions This work provides rationale for the translation of pathogen vaccines as FDA-approved clinical-grade DC activators which could be exploited as immune-stimulants for early phase trials.
Society for Immunotherapy of Cancer (SITC) checkpoint inhibitor resistance definitions: efforts to harmonize terminology and accelerate immuno-oncology drug development
Authors: Hussein A Tawbi, Ryan J Sullivan, David Feltquate, Theresa LaVallee, Naiyer A Rizvi, Elad Sharon, Jeffrey Sosman, Harriet M Kluger
Journal: Journal for ImmunoTherapy of Cancer (2023)

The need for solid clinical definitions of resistance to programmed death 1 or its ligand (PD-(L)1) inhibitors for clinical trial design was identified as a priority by the Society for Immunotherapy of Cancer (SITC). Broad consensus efforts have provided definitions for primary and secondary resistance and resistance after stopping therapy for both single-agent PD-(L)1 inhibitors and associated combinations. Validation of SITC’s definitions is critical and requires field-wide data sharing and collaboration. Here, in this commentary, we detail current utility and incorporation of SITC’s definitions and discuss the next steps both the society and the field must take to further advance immuno-oncology drug development.
Psilocybin therapy for females with anorexia nervosa: a phase 1, open-label feasibility study
Authors: Stephanie Knatz Peck, Samantha Shao, Tessa Gruen, Kevin Yang, Alexandra Babakanian, Julie Trim, Daphna M. Finn, Walter H. Kaye
Journal: Nature Medicine (2023)

Abstract Anorexia nervosa (AN) is a deadly illness with no proven treatments to reverse core symptoms and no medications approved by the US Food and Drug Administration. Novel treatments are urgently needed to improve clinical outcomes. In this open-label feasibility study, 10 adult female participants (mean body mass index 19.7 kg m − 2 ; s.d. 3.7) who met Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition (DSM-5) criteria for AN or pAN (partial remission) were recruited to a study conducted at an academic clinical research institute. Participants received a single 25-mg dose of synthetic psilocybin in conjunction with psychological support. The primary aim was to assess safety, tolerability and feasibility at post-treatment by incidences and occurrences of adverse events (AEs) and clinically significant changes in electrocardiogram (ECG), laboratory tests, vital signs and suicidality. No clinically significant changes were observed in ECG, vital signs or suicidality. Two participants developed asymptomatic hypoglycemia at post-treatment, which resolved within 24 h. No other clinically significant changes were observed in laboratory values. All AEs were mild and transient in nature. Participants’ qualitative perceptions suggest that the treatment was acceptable for most participants. Results suggest that psilocybin therapy is safe, tolerable and acceptable for female AN, which is a promising finding given physiological dangers and problems with treatment engagement. ClinicalTrials.gov identifier NCT04661514 .
Neoadjuvant adebrelimab in locally advanced resectable esophageal squamous cell carcinoma: a phase 1b trial
Authors: Jun Yin, Jingnan Yuan, Yunjin Li, Yong Fang, Ruoxi Wang, Heng Jiao, Han Tang, Shaoyuan Zhang, Siyun Lin, Feng Su, Jianmin Gu, Tian Jiang, Dong Lin, Zhiliang Huang, Chaoxiang Du, Kui Wu, Lijie Tan, Qing Zhou
Journal: Nature Medicine (2023)

Abstract Overall survival (OS) benefits of neoadjuvant immunotherapy remain elusive in locally advanced esophageal squamous cell carcinomas (ESCC). Here, we reported the results of a phase 1b trial of neoadjuvant PD-L1 blockade with adebrelimab in resectable ESCC. Patients received two neoadjuvant doses of adebrelimab followed by surgery. The primary endpoints were safety and feasibility; secondary endpoints included pathologic complete response (pCR) and OS. Our data showed the primary endpoints of safety and feasibility had been met. Common treatment-related adverse events were anorexia (32%) and fatigue (16%), without grade 3 or more adverse events. Of the 30 patients enrolled in the trial, 25 underwent successful resection without surgery delay and 24% had major pathologic responses including a pCR rate of 8%. The 2-year OS was 92%. Responsive patients had an immune-enriched tumor microenvironment phenotype, whereas nonresponsive patients had greater infiltration of cancer-associated fibroblasts at baseline. Clonotypic dynamics of pre-existing intratumoral T cells was a hallmark of responsive patients. These findings provide a rational for neoadjuvant anti-PD-L1 monotherapy as a therapeutic strategy for patients with resectable ESCC. ClinicalTrials.gov identifier: NCT04215471 .
First-line pyrotinib in advanced HER2-mutant non-small-cell lung cancer: a patient-centric phase 2 trial
Authors: Si-Yang Maggie Liu, Hai-Yan Tu, Xue-Wu Wei, Hong-Hong Yan, Xiao-Rong Dong, Jiu-Wei Cui, Zhen Zhou, Chong-Rui Xu, Ming-Ying Zheng, Yang-Si Li, Zhen Wang, Xiao-Yan Bai, An-Na Li, Yue-Li Sun, Jie Huang, Jia-Xin Lin, E. E. Ke, Bing-Fei Xu, Chang Lu, Yingying Du, Yuan Chen, Rui Ma, Bu-Hai Wang, Shun-Dong Cang, Bin-Chao Wang, Hua-Jun Chen, Jin-Ji Yang, Yangqiu Li, Qing Zhou, Yi-Long Wu
Journal: Nature Medicine (2023)
Pig-to-human heart xenotransplantation in two recently deceased human recipients
Authors: Nader Moazami, Jeffrey M. Stern, Karen Khalil, Jacqueline I. Kim, Navneet Narula, Massimo Mangiola, Elaina P. Weldon, Larisa Kagermazova, Les James, Nikki Lawson, Greta L. Piper, Philip M. Sommer, Alex Reyentovich, Daniel Bamira, Tajinderpal Saraon, Bernard S. Kadosh, Michael DiVita, Randal I. Goldberg, Syed T. Hussain, Justin Chan, Jennie Ngai, Thomas Jan, Nicole M. Ali, Vasishta S. Tatapudi, Dorry L. Segev, Shivani Bisen, Ian S. Jaffe, Benjamin Piegari, Haley Kowalski, Maria Kokkinaki, Jeffrey Monahan, Lori Sorrells, Lars Burdorf, Jef D. Boeke, Harvey Pass, Chandra Goparaju, Brendan Keating, David Ayares, Marc Lorber, Adam Griesemer, Sapna A. Mehta, Deane E. Smith, Robert A. Montgomery
Journal: Nature Medicine (2023)
Correcting the drug development paradigm for glioblastoma requires serial tissue sampling
Authors: Kirit Singh, Kelly M. Hotchkiss, Ian F. Parney, John De Groot, Solmaz Sahebjam, Nader Sanai, Michael Platten, Evanthia Galanis, Michael Lim, Patrick Y. Wen, Giuseppe Minniti, Howard Colman, Timothy F. Cloughesy, Minesh P. Mehta, Marjolein Geurts, Isabel Arrillaga-Romany, Annick Desjardins, Kirk Tanner, Susan Short, David Arons, Elizabeth Duke, Wolfgang Wick, Stephen J. Bagley, David M. Ashley, Priya Kumthekar, Roel Verhaak, Anthony J. Chalmers, Anoop P. Patel, Colin Watts, Peter E. Fecci, Tracy T. Batchelor, Michael Weller, Michael A. Vogelbaum, Matthias Preusser, Mitchel S. Berger, Mustafa Khasraw
Journal: Nature Medicine (2023)